The role of single cardiac cells in the origin of cardiac arrhythmias is to be studied. The transmembrane potential of single Purkinje fibers located in isolated specimens of canine cardiac tissue will be measured with glass microelectrodes. The primary objective is to study the influence of various agents and conditions on what are termed "slow responses". Slow responses are abnormal action potentials which result when the normal, rapid depolarization processes mediated by sodium ions become inactivated. It is believed that the occurrence of slow responses in single Purkinje fibers of the in situ heart may cause ventricular arrhythmias, especially those which often develop during myocardial infarction. It has been shown previously that low extracellular pH (6.0) is one condition capable of inducing slow responses in isolated Purkinje fibers. Ischemic cardiac tissues become acid in reaction; therefore, it is possible that excess hydrogen ions contribute to the production of slow responses and hence arrhythmias in the intact animal with myocardial ischemia. It is planned to study the effects on the transmembrane potentials of Purkinje fibers of low pH in combination with certain other alterations which also accompany myocardial ischemia. Hypoxia or changes in extracellular levels of potassium ions will be studied alone and then combined with low pH. The results may be useful in understanding the basic electrophysiological mechanisms responsible for the production of life-threatening arrhythmias during obstruction of a coronary artery.